Effects of rikkunshito, a kampo medicine, on quality of life after proximal gastrectomy.

Background: The loss of the gastroesophageal junction after proximal gastrectomy (PG) induces various gastrointestinal symptoms, such as regurgitation, anorexia, and body weight loss, leading to impairment of the postoperative quality of life. In the present study, we investigated the long-term quality of life and the effects of rikkunshito, a traditional Japanese medicine (kampo), on the gastrointestinal symptoms and plasma ghrelin levels in patients with gastric cancer who had undergone PG.

Methods: Nineteen patients who had undergone PG> 6 mo before entry into the present study were enrolled.

Adrenal cavernous hemangioma with subclinical Cushing's syndrome: report of a case.

Cavernous hemangioma of the adrenal gland is a rare tumor, which does not usually have endocrinological function. We report to our knowledge, the third documented case of a functioning adrenal hemangioma. Interestingly, this tumor indicated glucocorticoid hypersecretion, whereas the two previous cases showed mineralocorticoid hypersecretion.

Pancreatic endometrial cyst: report of a case.

A pancreatic endometrial cyst is an extremely rare disease. Since 1984, only 7 cases have been reported, including the current case. A 35-year-old woman with a history of recurrent severe left upper abdominal pain of 3 months' duration was found to have a cyst in the pancreatic body on the diagnostic imaging findings.

Diffusion-weighted magnetic resonance imaging for detecting lymph node metastasis of rectal cancer.

Background: Preoperative diagnosis of lymph node metastasis is important in determining the optimal therapy for rectal cancer. It has been shown that diffusion-weighted magnetic resonance imaging (DWI) is a useful tool for detecting malignant tumors.

Methods: One hundred twenty-nine consecutive patients with rectal cancer were examined with DWI + conventional (T1-weighted and T2-weighted) MRI and computed tomography (CT).

Suppression of colon cancer metastasis by Aes through inhibition of Notch signaling.

Metastasis is responsible for most cancer deaths. Here, we show that Aes (or Grg5) gene functions as an endogenous metastasis suppressor. Expression of Aes was decreased in liver metastases compared with primary colon tumors in both mice and humans.

Antibody responses against NY-ESO-1 and HER2 antigens in patients vaccinated with combinations of cholesteryl pullulan (CHP)-NY-ESO-1 and CHP-HER2 with OK-432.

Combination vaccines of the NY-ESO-1 protein complexed with cholesteryl pullulan (CHP), CHP-NY-ESO-1, and the truncated 146HER2 protein with CHP, CHP-HER2, were subcutaneously administered with the immuno-adjuvant OK-432 to eight esophageal cancer patients. Vaccination was well-tolerated. NY-ESO-1- and HER2-specific antibody responses were analyzed using the patients' sera and samples from previous single CHP-NY-ESO-1 or CHP-HER2 vaccine trial.

[Case report of gastric cancer patient who suffered life-threatening adverse events including severe myelosuppression during neoadjuvant chemotherapy with S-1 and CDDP combination].

Neoadjuvant chemotherapy has been a recent focus in the treatment for advanced gastric cancer. Although the preoperative chemotherapeutic regimen of S-1 and CDDP is regarded as effective, safe and well tolerable according to previous clinical study, we experienced a 74-year-old woman who suffered from life-threatening adverse events including severe myelosuppression during the neoadjuvant chemotherapy. Although the patient did not experience any severe adverse events during the first course of treatment, on day 18 of the second course of chemotherapy, she was hospitalized because of anorexia and severe dehydration, leading to following grade 4 leukopenia/neutropenia, bacteremia, and disseminated intravascular coagulation (DIC).

Intra-arterial infusion chemotherapy with 5-fluorouracil and cisplatin in advanced pancreatic cancer: a feasibility study.

Objective: Our aim was to examine the efficacy and tolerability of intra-arterial infusion chemotherapy with 5-fluorouracil (5-FU) and cisplatin in advanced pancreatic cancer.

Methods: Sixteen patients with unresectable locally advanced or metastatic pancreatic cancer (12 Stage IVa and 4 Stage IVb with liver metastasis) were enrolled. The catheter for intra-arterial infusion was placed at the position to distribute chemotherapeutic drugs to both the pancreatic tumor and the liver.

Preventive effect of a traditional herbal medicine, Hochu-ekki-to, on immunosuppression induced by surgical stress.

Purpose: To examine the effect of preoperative administering of a Japanese traditional herbal medicine, Hochu-ekki-to (TJ-41), on immunosuppression induced by surgical stress in patients with gastrointestinal malignancies.

Methods: To monitor the immune functions, the mitochondrial membrane potential (MMP) and natural killer (NK) cell activity prior to and following operation were measured in peripheral blood lymphocytes (PBL) in patients with (n = 20) or without (n = 27) the preoperative administering of TJ-41 for 7 days. The plasma catecholamine and interleukin (IL)-6 levels were also analyzed prior to and following the operation.

n-Propyl gallate activates hypoxia-inducible factor 1 by modulating intracellular oxygen-sensing systems.

HIF-1 (hypoxia-inducible factor 1) is a master regulator of cellular adaptive responses to hypoxia. The expression and transcriptional activity of the HIF-1alpha subunit is stringently controlled by intracellular oxygen tension through the action of prolyl and asparaginyl hydroxylases. In the present study we demonstrate that PG (n-propyl gallate) activates HIF-1 and expression of its downstream target genes under normoxic conditions in cultured cells and in mice.

Prognostic significance of the immediate early response gene X-1 (IEX-1) expression in pancreatic cancer.

Background: The immediate early response gene X-1 (IEX-1) is a stress-inducible protein that is involved in the regulation of cell proliferation and apoptosis. The aim of this study was to evaluate the prognostic significance of IEX-1 expression in pancreatic cancer.

Methods: IEX-1 protein expression was examined on paraffin-embedded specimens from 78 patients with pancreatic ductal adenocarcinoma using immunohistochemistry.

Uneventful splenectomy and cholecystectomy in a patient treated with anti-interleukin-6 receptor antibody therapy.

Introduction: Interleukin-6 (IL-6) is a multifunctional cytokine that regulates various aspects of the immune responses, acute phase reactions, and hematopoiesis. In rodent models, IL-6 has been suggested to be one of the essential mediators for optimal acute phase responses to infection and tissue damage. However, in humans, the roles of IL-6 in acute phase responses after surgery remain poorly understood.

SMAD4-deficient intestinal tumors recruit CCR1+ myeloid cells that promote invasion.

Inactivation of TGF-beta family signaling is implicated in colorectal tumor progression. Using cis-Apc(+/Delta716) Smad4(+/-) mutant mice (referred to as cis-Apc/Smad4), a model of invasive colorectal cancer in which TGF-beta family signaling is blocked, we show here that a new type of immature myeloid cell (iMC) is recruited from the bone marrow to the tumor invasion front. These CD34(+) iMCs express the matrix metalloproteinases MMP9 and MMP2 and the CC-chemokine receptor 1 (CCR1) and migrate toward the CCR1 ligand CCL9.

Retrospective analysis of 45 consecutive patients with advanced gastric cancer treated with neoadjuvant chemotherapy using an S-1/CDDP combination.

Background: Standard treatment for highly advanced gastric cancer (AGC) has not been established yet. Neoadjuvant chemotherapy (NAC) represents a promising approach, which may improve the prognosis of AGC. In this study, we analyzed the feasibility and efficacy of NAC with S-1 (TS-1)/cisplatin CDDP in order to design appropriate clinical trials for AGC.

The intravenous anesthetic propofol inhibits hypoxia-inducible factor 1 activity in an oxygen tension-dependent manner.

Hypoxia elicits a wide range of responses that occur at different organizational levels in the body. Hypoxia is not only a signal for energy conservation and metabolic change, but triggers expression of a select set of genes. The transcription factor hypoxia-inducible factor 1 (HIF-1) is now appreciated to be a master factor of the gene induction.

Ran, a small GTPase gene, encodes cytotoxic T lymphocyte (CTL) epitopes capable of inducing HLA-A33-restricted and tumor-reactive CTLs in cancer patients.

Purpose: The purpose is to identify a gene coding for tumor-associated antigen and peptide capable of inducing CTLs reactive to tumor cells with a HLA-A33-restricted fashion to provide scientific basis for specific immunotherapy to HLA-A33+ cancer patients.

Experimental Design: An expression gene-cloning method was used to identify the tumor-associated antigen gene. Northern blot analysis and immunohistochemistry were used to examine the mRNA and protein expression levels in various cells and tissues, respectively.

The inhibitory effect of sodium nitroprusside on HIF-1 activation is not dependent on nitric oxide-soluble guanylyl cyclase pathway.

Adaptation to hypoxia and maintenance of O(2) homeostasis involve a wide range of responses that occur at different organizational levels in the body. One of the most important transcription factors that activate the expression of O(2)-regulated genes is hypoxia-inducible factor 1 (HIF-1). Nitric oxide (NO) mediates a variety of biological effects including relaxation of blood vessels and cytotoxicity of activated macrophages.

Usefulness of 99mTc-sestamibi scintigraphy in suggesting the therapeutic effect of chemotherapy against gastric cancer.

Purpose: Imaging with (99m)Tc-sestamibi ((99m)Tc-MIBI) has been used to assess 170-kDa P-glycoprotein (P-gp) expression and predict chemotherapy responses in several types of malignancy, such as breast and lung cancers. The purpose of this study was to evaluate the relationship between (99m)Tc-MIBI accumulation in tumors and sensitivity to chemotherapy in gastric cancer patients.

Experimental Design: Thirty-six patients with advanced gastric cancer underwent (99m)Tc-MIBI scintigraphy before chemotherapy.

Pivotal role of CXCR3 in melanoma cell metastasis to lymph nodes.

Chemokines and their receptors play key roles in leukocyte trafficking and are also implicated in cancer metastasis to specific organs. Here we show that mouse B16F10 melanoma cells constitutively express chemokine receptor CXCR3, and that its ligands CXCL9/Mig, CXCL10/IP-10, and CXCL11/I-TAC induce cellular responses in vitro, such as actin polymerization, migration, invasion, and cell survival. To determine whether CXCR3 could play a role in metastasis to lymph nodes (LNs), we constructed B16F10 cells with reduced CXCR3 expression by antisense RNA and investigated their metastatic activities after s.

Immediate early response gene X-1, a stress-inducible antiapoptotic gene, encodes cytotoxic T-lymphocyte (CTL) epitopes capable of inducing human leukocyte antigen-A33-restricted and tumor-reactive CTLs in gastric cancer patients.

Peptide-based vaccine therapy, which is designed to elicit T-cell immunity against tumors, is an attractive approach for the treatment of cancer patients. To provide a scientific basis for peptide therapy, an increasing number of CTL-directed peptides have been identified, and some of them have been tried as antigen-specific immunotherapy in the past decade. Only a few studies, however, have been performed on such peptides restricted with alleles other than HLA-A2 and -A24.

Suppression of VEGFR-3 signaling inhibits lymph node metastasis in gastric cancer.

In gastric cancer, lymph node metastasis is one of the major prognostic factors and forms the basis for surgical removal of local lymph nodes. Recently, several studies have demonstrated that overexpression of lymphangiogenic growth factor VEGF-C or VEGF-D induces tumor lymphangiogenesis and promotes lymphatic metastasis in mouse tumor models. We examined whether these processes could be inhibited in naturally metastatic tumors by blocking of their cognate receptor VEGFR-3 signaling pathway.

CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression.

Background: Active suppression by CD4+CD25+ regulatory T cells plays an important role in the down-regulation of the response of T cells to foreign and self antigens. Experimental tumor models in mice revealed that regulatory T cells inhibit antitumor immune responses. The purpose of the current study was to demonstrate the possible involvement of CD4+CD25+ regulatory T cells in immune system impairment in patients with gastrointestinal malignancies.

Change in mitochondrial membrane potential in peripheral blood lymphocytes, especially in natural killer cells, is a possible marker for surgical stress on the immune system.

There is accumulating evidence that surgical stresses cause impairment of systemic immune responses, which may promote susceptibility to infection as well as growth of remnant cancer cells in cancer patients. Although alterations in numbers, populations, and functions of lymphocytes have been extensively studied to assess modulation of the immune system, the precise mechanisms of immunosuppression caused by surgical stresses have not been identified, nor have methods been developed to estimate the magnitude of surgical stresses on the immune system. In the present study, to evaluate the effects of surgical procedures on the immune system, the mitochondrial membrane potential (Delta Psi(m)) of peripheral blood lymphocytes (PBL) from 25 patients who underwent various types of operation was measured by flow cytometry using 3,3'-dihexiloxacarbocyanine iodide (DiOC(6)(3)) on the day before operation and on postoperative day (POD) 1, POD 3, and POD 7.